Acetylcholine → N-[2-[N-ethyl-N-[2-(2-fluoropyridin-3-yloxy)ethyl]amino]ethyl]phthalimide

HRID 2273615

反応式

HRID 2273615 の反応式
[CH2:1]([N:3]([CH2:7][CH2:8][N:9]1[C:13](=[O:14])[C:12]2=[CH:15][CH:16]=[CH:17][CH:18]=[C:11]2[C:10]1=[O:19])[CH2:4][CH2:5][OH:6])[CH3:2].[F:20][C:21]1[C:26](O)=[CH:25][CH:24]=[CH:23][N:22]=1.C1[C@@H](COC2C=CC=NC=2[18F])NC1.C(OCC[N+](C)(C)C)(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[CH2:1]([N:3]([CH2:7][CH2:8][N:9]1[C:13](=[O:14])[C:12]2=[CH:15][CH:16]=[CH:17][CH:18]=[C:11]2[C:10]1=[O:19])[CH2:4][CH2:5][O:6][C:26]1[C:21]([F:20])=[N:22][CH:23]=[CH:24][CH:25]=1)[CH3:2]

参加物

8

反応物 6

HCID 187AcetylcholineHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 4508602-Fluoro-3-(2S-azetidinylmethoxy)pyridine, F-18HCID 27627852-Fluoro-3-hydroxypyridineHCID 52951944N-[2-[N-ethyl-N-(2-hydroxyethyl)amino]ethyl]phthalimide

生成物 1

HCID 52951945N-[2-[N-ethyl-N-[2-(2-fluoropyridin-3-yloxy)ethyl]amino]ethyl]phthalimide収率 79%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of compound 3 (1.65 g, 6.29 mmol) in anhydrous tetrahydrofuran (THF, 80 mL) were successively added, under argon, 2-fluoro-3-hydroxypyridine (0.72 g, 6.37 mmol) (Dollé, F.; Valette, H.; Bottlaender, M.; Hinnen, F.; Vaufrey, F.; Guenther, I.; Crouzel, C. Synthesis of 2-[18F]fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine, a highly potent radioligand for in vivo imaging central nicotinic acetylcholine receptors. J. Label. Compds. Radiopharm. 1998, 41, 451-463), triphenylphosphine (1.65 g, 6.29 mmol) and dropwise diisopropyl azodicarboxylate (DIAD, 1.71 mL, 8.68 mmol). The mixture was stirred at room temperature for 24 h. The solvent was evaporated under reduced pressure and the residue was chromatographed (Al2O3, AcOEt) to give compound 4 (1.77 g, 4.95 mmol) as a yellow solid. Yield 79%; Rf (Al2O3, AcOEt) 0.84; mp 58-60° C.; IR (KBr) ν 1192, 1240, 1290, 1395, 1452, 1712, 2847, 2943 cm−1; 1H NMR (200 MHz, CDCl3) δ 1.29 (t, 3H, J=7.1 Hz), 2.97 (q, 2H, J=7.1 Hz), 3.14 (t, 2H, J=6.5 Hz), 3.24 (t, 2H, J=5.9 Hz), 4.08 (t, 2H, J=6.5 Hz), 4.31 (t, 2H, J=5.9 Hz), 7.35 (ddd, 1H, 5JH-F=0.9 Hz, J=4.8, 7.8 Hz), 7.52 (ddd, 1H, 4JH-F=10.0 Hz, J=1.6, 7.8 Hz), 7.97 (m, 3H), 8.07 (m, 2H); MS m/z 357 (M+, 1), 231 (15), 197 (100), 174 (23), 130 (10), 85 (17), 76 (10), 57 (45).

後処理

  1. customThe solvent was evaporated under reduced pressure
  2. customthe residue was chromatographed (Al2O3, AcOEt)

出典と根拠

ORDレコード
ord-9f1c188c56cc4f6784d9e45f805022a9
出典データセット
uspto-grants-2015_09
特許番号
US09125937B2

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